Home > Publications Database > Early-onset sleep alterations found in patients with amyotrophic lateral sclerosis are ameliorated by orexin antagonist in mouse models. > print

001     276320
005     20250411100806.0
024 7 _ |a 10.1126/scitranslmed.adm7580
|2 doi
024 7 _ |a pmid:39879320
|2 pmid
024 7 _ |a 1946-6234
|2 ISSN
024 7 _ |a 1946-6242
|2 ISSN
024 7 _ |a altmetric:173620079
|2 altmetric
037 _ _ |a DZNE-2025-00283
041 _ _ |a English
082 _ _ |a 500
100 1 _ |a Guillot, Simon J
|0 0000-0002-1623-7091
|b 0
245 _ _ |a Early-onset sleep alterations found in patients with amyotrophic lateral sclerosis are ameliorated by orexin antagonist in mouse models.
260 _ _ |a Washington, DC
|c 2025
|b AAAS
336 7 _ |a article
|2 DRIVER
336 7 _ |a Output Types/Journal article
|2 DataCite
336 7 _ |a Journal Article
|b journal
|m journal
|0 PUB:(DE-HGF)16
|s 1744358844_5312
|2 PUB:(DE-HGF)
336 7 _ |a ARTICLE
|2 BibTeX
336 7 _ |a JOURNAL_ARTICLE
|2 ORCID
336 7 _ |a Journal Article
|0 0
|2 EndNote
520 _ _ |a Sleep alterations have been described in several neurodegenerative diseases yet are currently poorly characterized in amyotrophic lateral sclerosis (ALS). This study investigates sleep macroarchitecture and related hypothalamic signaling disruptions in ALS. Using polysomnography, we found that both patients with ALS as well as asymptomatic C9ORF72 and SOD1 mutation carriers exhibited increased wakefulness and reduced non-rapid eye movement sleep. Increased wakefulness correlated with diminished cognitive performance in both clinical cohorts. Similar changes in sleep macroarchitecture were observed in three ALS mouse models (Sod1G86R, FusΔNLS/+, and TDP43Q331K). A single oral administration of a dual-orexin receptor antagonist or intracerebroventricular delivery of melanin-concentrating hormone (MCH) through an osmotic pump over 15 days partially normalized sleep patterns in mouse models. MCH treatment did not extend the survival of Sod1G86R mice but did decrease the loss of lumbar motor neurons. These findings suggest MCH and orexin signaling as potential targets to treat sleep alterations that arise in early stages of the disease.
536 _ _ |a 353 - Clinical and Health Care Research (POF4-353)
|0 G:(DE-HGF)POF4-353
|c POF4-353
|f POF IV
|x 0
536 _ _ |a 352 - Disease Mechanisms (POF4-352)
|0 G:(DE-HGF)POF4-352
|c POF4-352
|f POF IV
|x 1
588 _ _ |a Dataset connected to CrossRef, PubMed, , Journals: pub.dzne.de
650 _ 7 |a Orexins
|2 NLM Chemicals
650 _ 7 |a Melanins
|2 NLM Chemicals
650 _ 7 |a melanin-concentrating hormone
|0 67382-96-1
|2 NLM Chemicals
650 _ 7 |a Hypothalamic Hormones
|2 NLM Chemicals
650 _ 7 |a Pituitary Hormones
|2 NLM Chemicals
650 _ 7 |a Orexin Receptors
|2 NLM Chemicals
650 _ 7 |a Superoxide Dismutase-1
|0 EC 1.15.1.1
|2 NLM Chemicals
650 _ 2 |a Animals
|2 MeSH
650 _ 2 |a Amyotrophic Lateral Sclerosis: drug therapy
|2 MeSH
650 _ 2 |a Amyotrophic Lateral Sclerosis: pathology
|2 MeSH
650 _ 2 |a Amyotrophic Lateral Sclerosis: metabolism
|2 MeSH
650 _ 2 |a Orexins: metabolism
|2 MeSH
650 _ 2 |a Disease Models, Animal
|2 MeSH
650 _ 2 |a Humans
|2 MeSH
650 _ 2 |a Sleep: drug effects
|2 MeSH
650 _ 2 |a Male
|2 MeSH
650 _ 2 |a Melanins: metabolism
|2 MeSH
650 _ 2 |a Mice
|2 MeSH
650 _ 2 |a Wakefulness: drug effects
|2 MeSH
650 _ 2 |a Female
|2 MeSH
650 _ 2 |a Motor Neurons: drug effects
|2 MeSH
650 _ 2 |a Motor Neurons: pathology
|2 MeSH
650 _ 2 |a Motor Neurons: metabolism
|2 MeSH
650 _ 2 |a Hypothalamic Hormones: metabolism
|2 MeSH
650 _ 2 |a Pituitary Hormones: metabolism
|2 MeSH
650 _ 2 |a Orexin Receptors: metabolism
|2 MeSH
650 _ 2 |a Superoxide Dismutase-1: metabolism
|2 MeSH
650 _ 2 |a Superoxide Dismutase-1: genetics
|2 MeSH
650 _ 2 |a Mice, Transgenic
|2 MeSH
700 1 _ |a Lang, Christina
|0 P:(DE-2719)9002237
|b 1
700 1 _ |a Simonot, Marie
|0 0009-0001-6623-0648
|b 2
700 1 _ |a Beckett, Daniel
|0 0009-0004-8901-662X
|b 3
700 1 _ |a Lulé, Dorothée
|0 P:(DE-2719)9002172
|b 4
700 1 _ |a Balz, Luisa T
|0 0009-0002-8088-3386
|b 5
700 1 _ |a Knehr, Antje
|0 0009-0009-4039-4925
|b 6
700 1 _ |a Stuart-Lopez, Geoffrey
|0 0009-0009-0074-3019
|b 7
700 1 _ |a Vercruysse, Pauline
|0 0009-0009-3180-7847
|b 8
700 1 _ |a Dieterlé, Stéphane
|0 0009-0009-9951-3677
|b 9
700 1 _ |a Weydt, Patrick
|0 P:(DE-2719)9001116
|b 10
700 1 _ |a Dorst, Johannes
|0 P:(DE-2719)9001951
|b 11
700 1 _ |a Kandler, Katharina
|0 0000-0002-0785-379X
|b 12
700 1 _ |a Kassubek, Jan
|0 P:(DE-2719)9001967
|b 13
700 1 _ |a Wassermann, Laura
|0 0009-0004-4057-2975
|b 14
700 1 _ |a Rouaux, Caroline
|0 0000-0002-5724-2903
|b 15
700 1 _ |a Arthaud, Sébastien
|0 0000-0001-7271-5468
|b 16
700 1 _ |a Da Cruz, Sandrine
|0 0000-0003-1986-4565
|b 17
700 1 _ |a Luppi, Pierre-Hervé
|0 0000-0002-0503-423X
|b 18
700 1 _ |a Roselli, Francesco
|0 P:(DE-2719)2812851
|b 19
700 1 _ |a Ludolph, Albert C
|0 P:(DE-2719)2812633
|b 20
700 1 _ |a Dupuis, Luc
|0 0000-0002-0902-5824
|b 21
700 1 _ |a Bolborea, Matei
|0 0000-0003-2313-2770
|b 22
773 _ _ |a 10.1126/scitranslmed.adm7580
|g Vol. 17, no. 783, p. eadm7580
|0 PERI:(DE-600)2518839-2
|n 783
|p eadm7580
|t Science translational medicine
|v 17
|y 2025
|x 1946-6234
856 4 _ |u https://pub.dzne.de/record/276320/files/DZNE-2025-00283%20SUP.zip
856 4 _ |u https://pub.dzne.de/record/276320/files/DZNE-2025-00283_Restricted.pdf
856 4 _ |u https://pub.dzne.de/record/276320/files/DZNE-2025-00283_Restricted.pdf?subformat=pdfa
|x pdfa
909 C O |p VDB
|o oai:pub.dzne.de:276320
910 1 _ |a Deutsches Zentrum für Neurodegenerative Erkrankungen
|0 I:(DE-588)1065079516
|k DZNE
|b 1
|6 P:(DE-2719)9002237
910 1 _ |a Deutsches Zentrum für Neurodegenerative Erkrankungen
|0 I:(DE-588)1065079516
|k DZNE
|b 4
|6 P:(DE-2719)9002172
910 1 _ |a Deutsches Zentrum für Neurodegenerative Erkrankungen
|0 I:(DE-588)1065079516
|k DZNE
|b 5
|6 0009-0002-8088-3386
910 1 _ |a Deutsches Zentrum für Neurodegenerative Erkrankungen
|0 I:(DE-588)1065079516
|k DZNE
|b 6
|6 0009-0009-4039-4925
910 1 _ |a Deutsches Zentrum für Neurodegenerative Erkrankungen
|0 I:(DE-588)1065079516
|k DZNE
|b 10
|6 P:(DE-2719)9001116
910 1 _ |a Deutsches Zentrum für Neurodegenerative Erkrankungen
|0 I:(DE-588)1065079516
|k DZNE
|b 11
|6 P:(DE-2719)9001951
910 1 _ |a Deutsches Zentrum für Neurodegenerative Erkrankungen
|0 I:(DE-588)1065079516
|k DZNE
|b 12
|6 0000-0002-0785-379X
910 1 _ |a Deutsches Zentrum für Neurodegenerative Erkrankungen
|0 I:(DE-588)1065079516
|k DZNE
|b 13
|6 P:(DE-2719)9001967
910 1 _ |a Deutsches Zentrum für Neurodegenerative Erkrankungen
|0 I:(DE-588)1065079516
|k DZNE
|b 19
|6 P:(DE-2719)2812851
910 1 _ |a Deutsches Zentrum für Neurodegenerative Erkrankungen
|0 I:(DE-588)1065079516
|k DZNE
|b 20
|6 P:(DE-2719)2812633
913 1 _ |a DE-HGF
|b Gesundheit
|l Neurodegenerative Diseases
|1 G:(DE-HGF)POF4-350
|0 G:(DE-HGF)POF4-353
|3 G:(DE-HGF)POF4
|2 G:(DE-HGF)POF4-300
|4 G:(DE-HGF)POF
|v Clinical and Health Care Research
|x 0
913 1 _ |a DE-HGF
|b Gesundheit
|l Neurodegenerative Diseases
|1 G:(DE-HGF)POF4-350
|0 G:(DE-HGF)POF4-352
|3 G:(DE-HGF)POF4
|2 G:(DE-HGF)POF4-300
|4 G:(DE-HGF)POF
|v Disease Mechanisms
|x 1
914 1 _ |y 2025
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0200
|2 StatID
|b SCOPUS
|d 2024-12-20
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0300
|2 StatID
|b Medline
|d 2024-12-20
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0199
|2 StatID
|b Clarivate Analytics Master Journal List
|d 2024-12-20
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)1050
|2 StatID
|b BIOSIS Previews
|d 2024-12-20
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0160
|2 StatID
|b Essential Science Indicators
|d 2024-12-20
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)1190
|2 StatID
|b Biological Abstracts
|d 2024-12-20
915 _ _ |a WoS
|0 StatID:(DE-HGF)0113
|2 StatID
|b Science Citation Index Expanded
|d 2024-12-20
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0150
|2 StatID
|b Web of Science Core Collection
|d 2024-12-20
920 1 _ |0 I:(DE-2719)5000077
|k Clinical Study Center (Ulm)
|l Clinical Study Center (Ulm)
|x 0
920 1 _ |0 I:(DE-2719)1910001
|k AG Roselli
|l Metabolic Changes in Neurodegeneration
|x 1
980 _ _ |a journal
980 _ _ |a VDB
980 _ _ |a I:(DE-2719)5000077
980 _ _ |a I:(DE-2719)1910001
980 _ _ |a UNRESTRICTED

LibraryCollectionCLSMajorCLSMinorLanguageAuthor
Marc 21